title: [Type III familial hemophagocytic lymphohistiocytosis susceptibility gene UNC13D involves in homologous recombination repair].
abstract: This study was aimed to explore the pathogenesis of type III familial hemophagocytic lymphohistiocytosis (FHL3) via susceptibility gene UNC13D involving in homologous recombination repair (HRR) of DNA double-strand break (DSB). By means of DNA homologous recombination repair, the change of homologous recombination repair rate of normal control cells and DR-U2OS cells after down-regulation of UNC13D was detected; the UNC13D gene related function was explored. The results showed that DR-U2OS cells displayed a significant reduction in homologous recombination repair of DNA DSB after siRNA knockdown of UNC13D, compared to its normal control cell counterparts (P < 0.05), suggesting that UNC13D was involved in DNA double-stranded breakage repair. It is concluded that UNC13D gene mutation may be involved in the pathogenesis of FHL3 via its dual effects of both the cytotoxic granule exocytosis and decrease of homologous recombination repair rate after the DNA double-strand break, therefore, providing a new theoretical basis to reveal the pathogenesis of FHL3.
authors.affiliation: Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Li-Xian
authors.initials: LX
authors.lastname: Chang
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Zeng
authors.forename: Quan-Quan
authors.initials: QQ
authors.lastname: Zhou
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Zhou
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: An
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Yuan
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Zhu
mesh_terms: D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000145:classification / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D059767:Recombinational DNA Repair
chemical_list: D004268:DNA-Binding Proteins; D008565:Membrane Proteins; C507969:UNC13D protein, human